A previously reported high-performance liquid chromatographic (HPLC) method for indoprofen determination in physiological fluids was modified and extended to provide quantitative data on drug concentrations in human milk samples at a low nanogram per milliliter level. The reversed-phase HPLC technique was modified to give a better separation of the drug and milk components. To achieve the necessary cleanup for low level determination, the milk samples required protein precipitation, liquid-liquid drug extraction, and concentration. Excellent indoprofen recovery was obtained with this technique; the average recovery from 20 milk samples spiked with various nanogram drug levels was 95%. The analytical technique showed excellent reproducibility; the calibration solutions over 15 days had a relative standard deviation of 3.2%. Results for indoprofen levels in milk and plasma samples from seven subjects who received either a single or multiple oral drug dose are presented.