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H2-receptor antagonists have been shown to be effective in the suppression of nocturnal acidity. This double-blind, randomized, crossover Latin-square study of 24-h intragastric pH in 12 normal volunteers investigated the effect of large single-dose administration of misoprostol on intragastric acidity. Efficacy of 800 micrograms misoprostol h.s., 600 micrograms h.s., 400 micrograms h.s. and 800 micrograms after supper was compared to placebo and 200 micrograms misoprostol q.d.s. Twenty-four hour mean pH +/- s.d. was placebo 2.1 +/- 0.3, misoprostol 200 micrograms q.d.s. Twenty-four hour mean pH +/- s.d. was placebo 2.1 +/- 0.3, misoprostol 200 micrograms q.d.s. 2.2 +/- 0.3, 800 micrograms p.m. 2.6 +/- 1.1, 400 micrograms h.s. 2.6 +/- 0.7, 600 micrograms h.s. 2.6 +/- 0.4, 800 micrograms h.s. 2.6 +/- 0.5. The effect of misoprostol on gastric acidity was short and limited to the nocturnal period. Only misoprostol 800 micrograms and 600 micrograms reduced 24-h acidity compared to placebo (P less than 0.04).