Extended term, continuous measurement and observation of drug responses were performed to examine the feasibility of a custom-made whole-body plethysmograph for measuring respiratory function in unanesthetized, unrestrained monkeys. Using this apparatus, respiratory function (respiration rate, tidal volume, and minute volume) was observed for 23 hr in unanesthetized, unrestrained cynomolgus monkeys (Macaca fascicularis). The respiration rate, tidal volume, and minute volume in the light period (7:00 to 19:00) reached approximately 30% to 50% higher values than in the dark period (19:00 to 7:00), thus clearly exhibiting circadian variation in the cynomolgus monkey respiratory functions. Administration of morphine (10 mg/kg, s.c.) resulted in sustained reduction in tidal volume and minute volume, and ketamine (30 mg/kg [sub-anesthetic dose], i.m.) also produced sustained reduction in respiration rate, tidal volume, and minute volume. With dimorpholamine (1 mg/kg, i.v.) or caffeine (10 mg/kg, s.c.), respiration rate, tidal volume, and minute volume increased. Physiological saline (1 ml/kg, s.c. and 0.1 ml/kg, i.v.) and chlorpromazine (10 mg/kg, s.c.) produced no clear-cut changes in respiration rate, tidal volume, or minute volume. From the above results, we conclude that our custom-made whole-body plethysmograph is useful for measuring respiratory function in unanesthetized and unrestrained monkeys.