SUMMARY We gave 21 healthy young men 100 mg of hydrochlorothiazide daily to determine whether or not urinary detection of the drug was feasible as a measure of compliance on a standard antihypertensive regimen. All subjects took the drug daily for 6 days, after which they were divided into four groups with differing patterns of medication administration. Urine hydrochlorothiazide and creatinine measurements were obtained to validate the urinary hydrochlorothiazide-creatinine ratio (UHCR) as an accurate quantitative index of compliance. The subjects achieved a constant level of UHCR of 13 ± 3.0" within 48 hours of hydrochlorothiazide administration. The UHCR levels decreased to 5.0 ± 0.8 48 hours after discontinuation of the drug (p < 0.001). UHCR values in the range of 13 ± 6 indicate that the subject has ingested hydrochlorothiazide 24 hours previously. The UHCR is a potentially useful means of assessing compliance in hypertensive patients taking hydrochlorothiazide.