The anti-inflammatory effect of erythromycin was investigated using zymosan-induced peritonitis in mice. When mice were given erythromycin 10 mg/kg/day po for 28 days, a marked suppression of inflammatory responses, including the reduced influx of leucocytes, plasma exudation and prostaglandin E2 synthesis, was observed. However, neither a 7-day treatment with erythromycin nor a 28-day treatment with clindamycin suppressed the response. The anti-inflammatory activity induced after a 28-day treatment with erythromycin was comparable to the anti-inflammatory effect conferred by a 2-day treatment with dexamethasone 40 microgram/mouse/day. Thus, these data confirm previous studies which show that erythromycin can exert an anti-inflammatory effect when used over long periods of time.