Time course studies in rat adjuvant arthritis have shown that resident peritoneal macrophages synthesize large amounts of interleukin-1 (IL-1) on Day 10-11 postadjuvant immunization. Expression of Ia antigen on these macrophages increased rapidly between Day 15 to Day 20 postadjuvant treatment and remained at these high levels on Day 25. If these adjuvant immunized rats were treated with low doses of methotrexate, resident peritoneal macrophages appeared to synthesize lower amounts of IL-1 and their Ia expression was decreased. Methotrexate, in vitro, has no effect on lipopolysaccharide induced IL-1 synthesis by resident peritoneal macrophages.