The ability of lonidamine, an energolytic derivative of indazole-carboxylic acid, to modulate the cytotoxic activity of cisplatin was investigated on primary cultures obtained from 11 human ovarian carcinomas. A 72-h postincubation with lonidamine potentiated the activity of a 1-h cisplatin treatment. Statistical analysis of the dose-effect plots indicated that the interaction between the two drugs was synergistic in 4 tumors and additive in the remaining 7 tumors. The occurrence of the synergistic effect was independent of some biological characteristics of the tumor cell population, such as cell kinetics (as assessed by 3H-thymidine labeling index), DNA content and the expression of the putative factor of cisplatin resistance, glutathione-S-transferase pi.