The anti-proliferative activity of cocaine was determined in PC12 phenochromocytoma cells. The effects of nerve growth factor (NGF) and ganglioside GM1 (GM1) on the toxicity of this stimulant of abuse was examined over a period of 72 h. Cocaine (40 microM-320 microM) exhibited a dose-dependent inhibition of cellular proliferation as determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction. While NGF (100 ng/ml) and GM1 (100 microM) alone partially reversed the cocaine-induced inhibition of proliferation, the combination of NGF and GM1 afforded additional protection that was greater than that of either agent individually.