Morphine ED₅₀ values after either topical or systemic administration were determined in naive mice and in groups of mice that had received morphine chronically. ED₅₀ values and 95% confidence limits were determined with at least three doses of drug (n = 10–20/dose). In the systemic group, mice received morphine (5 mg/kg s.c.) daily for 4 days before testing on the fifth. The topical group was treated with a morphine solution (15 mM) daily for 2 days and the ED₅₀ value was determined on the 3rd day. At least three doses of morphine were used to calculate the ED₅₀values.