Ninety-one patients with advanced breast cancer failing adriamycin (ADR)-containing combination chemotherapy were treated with a combination of mitomycin C (MMC) and megestrol acetate. Congestive heart failure (CHF) occurred in 14 (15.3%) of 91 MMC-treated patients compared to three (3.4%) of 89 patients treated with similar ADR-containing combination chemotherapy without MMC (P = 0.01). The median time from the last dose of ADR to evidence of CHF was 8.5 months for the MMC group compared to 1.5 months for the other group. A significantly higher incidence of late onset of CHF implicates MMC as a possible cardiotoxic agent.