A rat gastric fistula preparation has been developed for the ready and safe administration of water-insoluble drugs. Graded doses of five sedative hypnotics - pentobarbital, secobarbital, methaqualone, diazepam and chloral hydrate - were studied using this preparation and a behavioral scale. The effect of these drugs on respiratory rate was also studied. The rat gastric fistula preparation is a stable one which allows the execution of crossover studies lasting for several months. Valid assays were obtained in comparisons of pentobarbital, secobarbital and methaqualone using both total behavior scale scores (BSS) and depression of respiratory rate. Secobarbital was equipotent to and methaqualone one-fourth as potent as pentobarbital. The slope of the chloral hydrate BSS dose-response line was statistically significantly steeper than that of pentobarbital. The diazepam BSS dose-response line was not only significantly less steep than that of pentobarbital but a plateau was seen. Neither chloral hydrate nor diazepam produced a dose-related depression of respiratory rate. The rat gastric fistula preparation has thus proved useful in characterizing the pharmacologie profiles, dose-response relationship and relative potencies of sedative hypnotics.