The disposition of hydroxychloroquine enantiomers has been investigated in nine patients with rheumatoid arthritis following administration of a single dose of the racemate. Blood concentrations of (-)-(R)-hydroxychloroquine exceed those of (+)-(S)-hydroxychloroquine following both an oral and intravenous dose of the racemate. Maximum blood concentrations of (-)-(R)-hydroxychloroquine were higher than (+)-(S)-hydroxychloroquine after oral dosing (121 +/- 56 and 99 +/- 42 ng/ml, respectively, P = 0.009). The time to maximum concentration and the absorption half-life, calculated using deconvolution techniques, were similar for both enantiomers. The fractions of the dose of each enantiomer absorbed were similar, 0.74 and 0.77 for (-)-(R)- and (+)-(S)-hydroxychloroquine, respectively (P = 0.77). The data suggest that absorption of hydroxychloroquine is not enantioselective. The stereoselective disposition of hydroxychloroquine appears to be due to enantioselective metabolism and renal clearance, rather than stereoselectivity in absorption and distribution.