Lonidamine was studied in 31 patients with different types of advanced cancer. With one exception, patients were pretreated. Lonidamine was given at 6 dosage levels from 180 to 520 mg/m2 for at least 28 days. No toxicity on hematopoietic function was observed. Side effects consisted mostly in musculoskeletal discomfort, testicular pain in males and a reversible ototoxicity. In 2 patients conjunctivitis and photophobia occurred. Plasma Lonidamine levels were measured in 14 patients. Peak concentrations were observed from 1 to 2 h after administration and ranged from 3 to 35 micrograms/ml. Objective antitumoral effects were observed in only 2 patients with mycosis fungoides; a 3rd patient with mycosis fungoides was considered to have stable disease.