1. A human neuroblastoma cell line, SH-SY5Y, was used to determine the effects of delta-9-tetrahydrocannabinol (THC) on microtubule-associated tau protein. 2. After 48-hr treatment, THC (10(-9) M) decreased 50 kD tau protein in the cytoplasmic (supernatant) fraction, and in the membrane (pellet) fraction the drug (10(-7) M) also decreased 50 kD tau protein. 3. This reduction in tau protein was accompanied by a 27% reduction (P < 0.05) in the membrane (pellet) total protein after (10(-7) M) THC and a 28% increase (P < 0.02) in cytoplasmic (supernatant) total protein after 10(-9) M THC.