This study was designed to explore whether blood O2 affinity and hypoxic ventilation (HV) behave as independent physiological variables. The experimental model was applied using phytic acid, known to decrease blood oxygen affinity, in rats (low Hb-O2 affinity) and guinea pigs (high Hb-O2 affinity). Baseline P50 and ventilation were significantly lower in guinea pigs than in rats. After administration of phytic acid for 3 weeks, P50 increased significantly more in guinea pigs than in rats. As previously shown, HV was substantially lower in control guinea pigs than in control rats. Guinea pigs with low Hb-O2 affinity induced by phytic acid did not modify their HV significantly. The percent change of ventilation was not significantly different in guinea pigs as compared with rats. At the same level of acute hypoxia, HV was significantly lower in treated guinea pigs than in rats. When the baseline P50 was relatively high (rats), the administration of this pharmacologic agent changed P50, but to a lesser degree than when baseline values were relatively low (guinea pigs). HV and P50 seem to behave as rather independent biological parameters, at least under experimental conditions. © 1995.