Propoxyphene (P) and norpropoxyphene (NP) excretion in breast milk was studied in six healthy nursing mothers. Concentrations of P and NP in breast milk and plasma were quantitated by an HPLC method. Plasma P t 1/2 s in mothers averaged 4.40 hr. P and NP breast milk concentrations generally followed plasma levels. NP/P averaged 2.69 in plasma and 2.73 in breast milk. While there was substantial inter- and intrasubject variability, the ratio of drug in the milk and plasma averaged 0.417 and 0.382 for P and NP. These similarities in distribution in breast milk were also reflected in elimination. Clearances of P and NP in milk were of the same order (3.97 ml/hr) as were elimination t 1/2 s in milk in most subjects (mean = 3.68 hr for P and 5.49 hr for NP). Approximately twice as much NP was excreted in the milk, primarily because of the higher NP levels in plasma. Clearance of P and NP in breast milk also correlated strongly with breast milk volume. While little information is available concerning P and NP disposition in neonates, dosage estimates based on kinetic and pharmacologic assumptions suggest that the estimated amounts consumed by the neonate after the mother is given the recommended dose of the drug are not likely to result in toxic plasma levels.