The disposition of 40 mg of d-methadone HCl was studied in New Zealand White rabbits. After an intravenous infusion to male rabbits, the beta phase half-life was 106 +/- 21 min and the apparent volume of distribution was 12.6 liters/kg b.w. After an i.m. injection, the peak drug concentration in arterial blood (1.02 microgram/ml) occurred 10 min after the injection, whereas the peak concentration in semen (2.58 microgram/ml) occurred 140 min later. The semen/blood drug concentration ratio was 6.8 at 150 min after the injection. The concentration of d-methadone was measured in blood, spleen, liver, lung, prostate, seminal vesicle, testis and heart 130 minutes after an i.m. dose. All tissues had drug levels that exceeded the concentration in blood (0.42 microgram/ml). The concentrations in lung (33.5 microgram/g), kidney (15.2 microgram/g) and spleen (30.6 microgram/g) were particularly elevated. After intravaginal implantation, d-methadone was rapidly absorbed into the systemic circulation of female rabbits; the peak drug level in blood (0.94 microgram/ml) occurred 60 min after drug administration.