The purpose of this clinical study was to determine the effect of intralesional vinblastine administration on intraoral Kaposi's sarcoma (KS) in AIDS patients. One hundred and forty-four KS lesions in 50 HIV-positive homosexual males (mean CD4 count 64/mm3) were treated periodically with intralesional vinblastine injection (0.1 mg/cm2) until lesion resolution or no further reduction in lesional area. The most common lesion sites were: palate 56% (hard palate 42%, soft palate 14%); gingiva 22% (maxillary 15%, mandibular 7%); and maxillary tuberosity 6%. The mean lesion area was 4.6 cm2 (range = 0.1-35 cm2). Complete resolution occurred in 74%. The mean reduction in lesional area was 93% for all lesions. Lesions with only a partial response (26%) to vinblastine had a mean reduction in the lesional area of 69%. The mean number of treatments was 2.4 (range = 1-6). The recurrence rate was 26% with a mean disease-free period of 12.9 weeks. Recurrence rates were highest for nodular (40%) and purple macular lesions with focal nodularity (36%). The most frequent complications were transient pain (72%), superficial mucosal ulceration (22%) and transient paresthesia (12%). Intralesional vinblastine administration produced complete resolution in a substantial number of intraoral KS lesions and represents a well-tolerated treatment regimen for localised control of intraoral KS lesions. Owing to a 25% recurrence rate, re-evaluation is necessary for treatment of recurrent and new Kaposi's sarcoma lesions.