The present study was designed to evaluate some immunological and cytogenetic effects of Micromeria myrtifolia extracts (methanol and hexane) and methotrexate in albino male mice (in vivo). The immunological parameters were total and absolute counts of leucocytes, total serum IgG level and metaphase index of bone marrow and spleen cells, while cytogenetic evaluations included micronucleus formation in polychromatic erythrocytes of bone marrow and sperm-head abnormalities. Additionally, a chemical detection of flavonoids, polysaccharides and alkaloids in methanol extract, and steroids in hexane extract was also carried out. The evaluations included two main parts. In part I, the immunological and cytogenetic effects of both extracts and methotrexate were carried out. Two doses (200 and 600 mg/kg) of the extracts and one dose of methotrexate (0.33 mg/kg) were investigated, in which the materials was given for seven days (single dose/day) and the evaluation was carried out on day eight. In part II, interactions (pre- and post-treatments) between the two doses of the extracts and methotrexate were evaluated. In both cases, the extracts and methotrexate were administrated orally. The following results were obtained: 1. The chemical detection revealed that the methanol extract was positive for flavonoids and polysaccharides and it was negative for alkaloids, while the hexane extract was positive for steroids. 2. Methotrexate declared clear immune suppressive and mutagenic effects as judged by the investigated parameters. Reduced indices of metaphase in bone marrow and spleen cells, and increased frequency of micronucleus formation were observed. Additionally, the total count of leucocytes and the absolute count of lymphocytes and monocytes, as well as, the total IgG serum level were significantly decreased as compared with the negative control. 3. The results of part I indicated that M. myrtifolia extracts modulated the values of the investigated immunological parameters positively as compared to negative (distilled water and olive oil) and positive (methotrexate) controls. Similarly, the spontaneous formation of micronuclei and sperm-head abnormalities was significantly decreased. In both cases the effect was dependent on dose, as well as, the type of extract. In this regard the low dose (200 mg/kg) was better than the dose 600 mg/kg, and the hexane extract was more effective than the methanol extract, although, the effect was subjected to the parameter of investigation. 4. The results of part II confirmed the observations made in part I, and the two doses of methanol and hexane extracts showed a significant efficiency in protecting the immune system and the genetic make-up from the immune suppressive and mutagenic effects of methotrexate. In this regard, the pretreatment with the extract was more effective than post-treatment.