The question of chromosomal damage subsequent to methotrexate treatment of psoriasis was studied by examining the metaphase chromosomes in a total of 6,200 leukocytes from nine methotrexate-treated psoriatics, nine drug-free psoriatics, and ten healthy adults. No biologically or statistically significant increase in chromosomal abnormalities could be detected at the various methotrexate doses used in these patients. Subsequently, in an in vitro experiment chromosomal damage was observed when methotrexate was added to the culture medium at three and 30 times the peak plasma concentrations achieved after a large single and small multiple oral doses of methotrexate. Since this could possibly reflect the in vivo situation at higher doses, conservative methotrexate dosages should be used in the treatment of psoriasis until the cytogenetic effects of higher doses are known.