The diethylaminoester of flavone acetic acid (LM985) is a new anticancer agent with curative effects against slow growing murine tumors. Thirty-one adult patients with solid tumors received a total of 57 courses of LM985 given on days 1 and 8 every 4 weeks. The drug was given as a short infusion (1-2 hr) at doses ranging from 120 to 1900 mg/sq.m/day. The dose-limiting toxicity consisted of acute expressive aphasia; this neurotoxicity usually appeared at the end of the infusion and resolved spontaneously within a few minutes to 1 hr after the end of the infusion. In some patients, neurotoxicity was avoided by reducing the infusion rate. Neurotoxicity was observed in 5 out of 6 patients receiving 960 mg/sq.m over 1 hr and in 3 out of 3 patients receiving 1900 mg/sq.m over 2 hr. The drug did not induce any significant myelosuppression. Other side-effects were very mild and consisted mainly of occasional nausea and/or vomiting at all dose levels. One patient with breast cancer resistant to several hormonal and chemotherapy regimens had stable disease for 6 months. LM985 was detected in plasma in very small concentrations (0-2.5 micrograms/ml) but there was extensive formation of flavone acetic acid (peak concentration ranging between 8.3 and 64 micrograms/ml). A dose of 1500 mg/sq.m on days 1 and 8 every 4 weeks could be recommended for phase II studies with LM985; however, since LM985 is a prodrug of flavone acetic acid, phase II studies with LM985 should not be activated prior to the completion of the ongoing phase I trials with flavone acetic acid, which may be devoid of the acute toxicity of LM985.