This study assessed the duration of action of single doses of ranitidine (75 mg), cimetidine (200 mg), or placebo on intragastric acidity in healthy subjects. When dosed with placebo, mean daytime intragastric acidity (0–10 hr after dose) was 37.62 mmol/liter, decreasing to 17.21 mmol/liter (mean decrease 59%; P < 0.001 vs placebo) and 25.06 mmol/liter (mean decrease 35%; P < 0.001 vs placebo) when treated with ranitidine and cimetidine, respectively. Ranitidine inhibited intragastric acidity to a greater degree than cimetidine (P < 0.001). Mean nighttime (10–20 hr after-dose) intragastric acidity when dosed with placebo was 34.37 mmol/liter, decreasing to 29.06 mmol/liter (mean decrease 18%; P = 0.027 vs placebo) when dosed with ranitidine and remaining virtually unchanged at 33.85 mmol/liter (mean decrease 2%; NS vs. placebo) when dosed with cimetidine. Ranitidine inhibited acidity to a greater degree than cimetidine (P = 0.043). The inhibitory effect of ranitidine, 75 mg, on intragastric acidity can be detected from 0–15 hr after an oral dose. Cimetidine 200 mg has little inhibitory effect beyond 10 hr.