Our aim was to simultaneously investigate 2 techniques for in vivo sampling of peripheral compartment pharmacokinetics after systemic administration of acetylsalicylic acid. Ten volunteers were given 2 g acetylsalicylic acid orally. Blood samples and dialysates from 4 microdialysis probes inserted in the dermis of the forearm were collected for 5 h and suction blisters were raised 1-3 h after dosing. In microdialysates, both acetylsalicylic acid and the metabolite salicylic acid were measurable in the absence of hydrolysing enzymes. The mean Cmax (maximum concentration) of total, unbound salicylic acid was 9.5 microg/ml in microdialysates, 13.2 microg/ml in suction blister fluid and 56.5 microg/ml in plasma. Mean Tmax (time to Cmax) for salicylic acid was 188 and 161 min in plasma and microdialysates, respectively. The dermis-to-plasma Cmax ratio was 0.16+/-0.04 (mean +/- SD) by microdialysis sampling and 0.25+/-0.09 by the suction blister fluid method. Close correlations (p<0.01) were found between Cmax of salicylic acid in microdialysates and plasma, and between Cmax of salicylic acid in suction blister fluid and plasma. The 2 techniques were in excellent accordance with even closer correlation between maximum concentrations obtained by microdialysis and suction blister fluid sampling (p<0.001). However, comparing the tolerability of the sampling procedure, ease of analysis, and detail in chronology, microdialysis is superior for sampling in vivo pharmacokinetics in the dermis.