The effect of methotrexate (MTX) treatment on patients with rheumatoid arthritis on interleukin 1 (IL-1) was evaluated. Eight patients received a weekly MTX dose of 7.5 mg for 6 weeks; none received concomitant corticosteroids. Peripheral blood was obtained 1 day before and 1 day after their weekly MTX dose at Week 1 and 6, isolated monocytes stimulated ex vivo with 1 mg/ml zymosan for 18 h and IL-1 measured by bioassay. Serum and plasma IL-1 levels were measured by immunoassay. Four patients manifested a sharp decrease in IL-1 production 6 weeks after MTX administration associated with a decrease in the number of painful but not swollen joints. No effect on blood levels was observed. Our results suggest that MTX may affect IL-1 production and IL-1 mediated events in some patients.