Plasma salicylate concentrations during multiple-dose administration of an uncoated and a sustained-release aspirin preparation were compared. Eight healthy adult subjects were given aspirin 2.6 g/day as sustained-release and uncoated tablets in two and four divided doses, respectively, for five-day periods in a crossover design. Treatment regimens were compared on the basis of five plasma salicylate concentrations measured during the fourth and fifth days of drug administration. Although there was considerable intersubject variation, no significant differences in salicylate concentrations (p less than or equal to 0.05) were found between treatments at any sampling time using the Wilcoxon signed-rank test or analysis of variance. Sustained-release aspirin preparations are capable of producing plasma salicylate concentrations comparable with those produced by uncoated aspirin tablets administered more frequently.