The efficacy and safety of topical treatment for external condylomata acuminata with either self-applied 0.5% podophyllotoxin (PT) or hospital-applied 25% podophyllin (PODO) solution was compared in 138 males and 67 females in an open multicentre study. After one week of treatment, wart clearance was observed in 53% of males and 37% of females in the PT group as compared with 19% of males and 19% of females in the PODO group (P < 0.001 in males; P = 0.13 in females). At 5 weeks after commencing treatment, clearance of warts had been achieved in 86% males and 72% females in the PT group as compared with 78% of males and 62% females in the PODO group (P = 0.08 in males; P = 0.14 in females). Treatment had cleared 81% of 180 treated sites in all PT recipients as compared with 61% of 95 treated sites in all PODO recipients (P < 0.001). The increased speed of action of PT was associated with an increased incidence of symptoms and signs of inflammation at treatment sites in both males and females (P < 0.001). These were generally mild, did not interfere with continuing treatment, and were more frequent in those patients whose warts were eradicated most rapidly. Home-based treatment with 0.5% podophyllotoxin lotion in appropriately instructed patients of either sex is superior in efficacy to outpatient applied 25% podophyllin and has the potential to reduce the number of hospital attendances required in genital wart eradication.