AbstractThe antioedematogenic activity of two natural pregnane compounds fromMandevilla velutinawas evaluated against croton oil‐induced ear oedema in mice. For comparison the effects of nonsteroidal (indomethacin, phenidone and BW 755C) and steroidal (dexamethasone) antiinflammatory drugs were analysed. The purified compounds fromM. velutinaMV8612 (3 and 30 mg/kg, i.p.) and to a lesser extent MV8608 (30 and 100 mg/kg; i.p.), given 30 min prior to the croton oil, significantly inhibited this oedema, maximal inhibition (MI) of 53% and 26%, respectively. However, given orally 180 min after, neither compound had any effect. Compound MV8612 but not MV8606 (200–600 μg/ear) given 180 min after the irritant significantly inhibited croton oil‐induced oedema, MI of 29%. Indomethacin given topically (0.05–0.2 mg/ear) 180 min after, but not orally (1–10 mg/kg), significantly inhibited this oedema, MI of 30%, while phenidone administered either orally (100 and 300 mg/kg) or topically (2 mg/ear) 180 min after caused partial inhibition, MI of 24% and 18%, respectively. BW 755C, given topically (0.1 and 0.5 mg/ear) but not orally (10–300 mg/kg) 180 min after, was also effective in inhibiting croton oil oedema, MI of 18%. Dexamethasone given either topically (0.05–0.2 mg/ear) or orally (0.25‐1 mg/kg) 30 and 60 min prior potently inhibited croton oil oedema, MI of 86% and 79%, respectively. These results indicate that the natural compounds MV8612 and to a lesser extent MV8608 isolated fromM. velutina, besides their antibradykinin activity, exhibited both topical and systemic long‐lasting antioedematogenic effects against croton oil‐induce