To determine if laboratory strains of guinea pigs bred at sea level (SL) are "pre-adapted" to high altitude (HA), we raised litter-matched weanling Hartley guinea pigs for 4 months at SL, intermediate altitude (IA, 1250 m) or HA (3800 m) and exposed them acutely to 100, 21 and 12% inspired 02 at their respective altitude of residence. Control animals raised at SL were also exposed acutely to 10 and 8% inspired O-2. In awake spontaneously breathing guinea pigs raised at SL, resting minute ventilation and tidal volume increased significantly when inspired O-2 tension fell below about 60 mmHg. In guinea pigs raised at IA or HA, ventilation was higher at any given inspired O-2 tension in direct relationship to the altitude of residence. Resting hematocrit was also higher in animals raised at HA than at SL. We conclude that the pattern of ventilatory acclimatization to HA exposure in Hartley guinea pigs is similar to that in laboratory rats and human lowlanders; therefore laboratory guinea pigs are not pre-adapted and are suitable animals for the study of adaptation to high altitude. (C) 2004 Elsevier B.V. All rights reserved.