Plasma concentrations of etretinate (E), acitretin (A) and 13-cis-acitretin (13-cis A) were measured using a reverse phase HPLC assay in patients with psoriasis during 24h after the first dose (0.8 mg/kg) and after 3 weeks (group A), and in a second group with various skin diseases (B) under long-term treatment after 3 months. Group A (n = 8) showed median peak plasma concentration levels (Cmax) 578 ng/ml for E. and 161 ng/ml for A 4h after dosing (tmax). The plasma concentration profile of 13-cis A. was plateau-like with Cmax-levels of 138 ng/ml after 4 to 10 hours. In group B treated with 0.3 to 0.4 mg/kg etretinate a trend to increased Cmax-values with 123 ng/ml for E., 44 ng/ml for A. and, more pronounced, 210 ng/ml for 13-cis A. occurred (steady state). In a third group C (n = 17) it was found that after an eight month treatment free period measurements of the 13-cis A. plasma concentration are more sensitive than that of E. or A. Comparing the pharmacokinetics in two patients with the same clinical conditions under E. and A., resp., two fold higher Cmax-values of A. after A. were found than for A. after E. However, 13-cis A. values were higher after E. than after A. Our observations have shown that the metabolisation of A. to 13-cis A. may be disturbed and the clinical efficacy may appear only after dramatic increase of the oral doses. Routine monitoring of plasma concentration profiles of oral retinoids and their metabolites under short or long-term treatment enable us to early identify and understand better the so-called "non-responders", either due to a disturbed metabolism of retinoids or to non-compliance. Furthermore, monitoring of 13-cis A in plasma after cessation of treatment with E. or A. in women in childbearing age seems to be more sensitive than measurement of plasma levels of E. or A. These measurements are helpful for defining the strategy of oral retinoid therapy and for reliable information of females who wish to become pregnant after interrupting the drug.