The effect of activated charcoal on fluoxetine (40 mg) absorption, with special reference to delayed charcoal administration, was investigated in a randomized study with four parallel groups of eight Healthy volunteers. The first group ingested fluoxetine on an empty stomach with water only (control). The second group received 25 g of activated charcoal as a suspension immediately after fluoxetine. The third and fourth groups took fluoxetine with water and received 25 g of charcoal 2 or 4 hr after fluoxetine. Timed blood samples were taken and plasma fluoxetine and norfluoxetine concentrations were measured by GC for 96 hr. When charcoal was administered immediately after fluoxetine, the AUC (0-96 hr) of fluoxetine was reduced by more than 96% (P < 0.0005) and the Cmax by more than 98% (P < 0.0005). The reduction in the AUC (0-96 hr) and Cmax of norfluoxetine was similar to that of fluoxetine. When the administration of charcoal was delayed 2 or 4 hr, there was a non-significant mean reduction of 16% and 23% in the AUC (0-96 hr) of fluoxetine. Similarly, the Cmax was not significantly reduced by charcoal given 2 or 4 hr later. Also, the half-life of fluoxetine was not significantly reduced (by 25%) by the late administration of charcoal. We conclude that activated charcoal, ingested immediately after fluoxetine, practically completely prevents the gastrointestinal absorption of fluoxetine. However, regardless of the relatively slow absorption of fluoxetine, delaying charcoal administration 2-4 hr greatly reduces its antidotal efficacy.