Compartmental models were used to investigate the pharmacokinetics of intravenous (i.v.), oral (p.o.), and topical (TOP) administration of dimethyl sulfoxide (DMSO). The plasma concentration-time curve following a 15-min i.v. infusion of DMSO was described by a two-compartment model. Median and range of alpha (t1/2α ) and beta (t1/2β ) half-lives were 0.029 (0.026-0.093) and 14.1 (6.6-16.4) hr, respectively. Plasma concentration-time curves of DMSO following p.o. and TOP administration were best described by one-compartment absorption and elimination models. Following the p.o. administration, median absorption (t1/2ab ) and elimination (t1/2e ) half-lives were 0.15 (0.01-0.77) and 15.5 (8.5-25.2) hr, respectively. The plasma concentrations of DMSO were 47.4-129.9 μg/ml, occurring between 15 min and 4 hr. The fractional absorption (F) during a 24-hr period was 47.4 (22.7-98.1)%. Following TOP administrations, the median t1/2ab and t1/2e were 1.2 (0.49-2.3) and 4.5 (2.1-11.0) hr, respectively. Plasma concentrations were 1.2-8.2 μg/ml occurring at 2-4 hr. Fractional absorption following TOP administration was 0.48 (0.315-4.4)% of the dose administered. Clearance (Cl) of DMSO following the i.v. administration was 3.2 (2.2-6.7) ml hr-1  kg-1 . The corrected clearances (ClF ) for p.o. and TOP administrations were 2.9 (1.1-5.5) and 4.5 (0.52-18.2) ml hr-1  kg-1 .