The effects of multiple-dose activated charcoal administration on the absorption of orally administered salicylate were evaluated in a simulated overdose model. Thirteen adult volunteers were each given 24 81-mg aspirin tablets during a control phase, and during three randomized treatment periods the volunteers received 50 g activated charcoal for one, two, or three doses (separated by four hours). The control phase and treatment periods were separated by a one-week interval. Urine was collected for 48 hours to determine percent total salicylate excretion. Ten subjects completed all four phases of the study. Mean +/- SD percent recovery of salicylate from urine was: control, 91.0 +/- 6.12; one-dose charcoal, 68.3 +/- 12.46; two-dose charcoal, 65.9 +/- 13.48; and three-dose charcoal, 49.2 +/- 12.48. Each charcoal treatment significantly lowered the absorption of aspirin as compared with the control (P less than .01). There was no significant difference between one-dose and two-dose charcoal regimens. There was a statistically significant decrease in salicylate absorption with the three-dose charcoal regimen as compared to one-dose and two-dose regimens (P less than .01). We conclude that activated charcoal is effective in inhibiting absorption of orally administered salicylate, in a small-dose aspirin ingestion model, with a three-dose multiple charcoal regimen being superior to either single-dose or two-dose regimens.