Thirty-nine previously treated patients with metastatic breast cancer were treated in a partially randomized study evaluating VP-16 [4-demethyl-epipodophyllotoxin-B-D-ethylidene glucoside] and the combination of vincristine (VCR) and adriamycin (ADR). Of the 19 patients treated with VP-16 initially, 2 had partial remissions. No responses were noted in 11 patients who crossed over after failing VCR plus ADR. Of the 20 patients treated with VCR plus ADR initially, 4 patients had partial responses. An additional 2/15 patients responded on crossover after failing initially on VP-16. No significant differences in time to last follow-up or death could be detected between the 2 treatment programs.