An improved method for the analysis of retinoids in mouse plasma allows quantification of all-trans-retinoic acid (RA) and N-(2-hydroxyethyl)retinamide (NHERA) in amounts as low as 2 ng/ml (7 X 10(-9) M), the approximate endogenous concentration of RA. The procedure, involving solid-phase extraction and reverse-phase HPLC, can be used for rapid processing of large numbers of samples. With this procedure, we have determined the terminal half-life for RA (0.5 hr) and have confirmed the half-life for NHERA (3.6 hr) in the plasma of mice dosed orally. We have also noted that the serum content of retinol is temporarily reduced following dosing with RA, but not with NHERA.