The heart rate response to isoproterenol (HR-Iso), density and affinity (k(d)) of β-adrenergic (β-AR) and muscarinic (M2) receptors were compared among three rodents with different generation-life histories of confinement and of high altitude exposure. The European guinea pig (Cavia porcellus) (EGp), a laboratory animal that arrived in Europe after the Spanish Conquest of South America and the Peruvian guinea pig (C. porcellus) (PGp), a semi-wild animal that came from the altiplano to sea level at least 25 generations ago, were used for intra-species comparison. Wistar rats (WR) were used for inter-species comparison as representative of a typical sea level laboratory animal. The HR-Iso was lower in EGp than in the PGp. The PGp showed the highest β-AR density (P<0.0005) and the highest β-AR k(d) values (P<0.0005) when compared to both EGp and WR groups (β-AR B(max) (fmol mg-1 prot), WR, 19±4; Egp, 34±10; PGp, 74±15. β-AR k(d) (pM), WR, 24±10; Egp, 17±7; PGp, 39±14). In contrast, PGp showed lower M2 receptor density values than the EGp (P<0.0005). The WR had the highest M2 receptor densities (M2 B(max) (fmol mg-1 prot), WR, 188±15; Egp, 147±9; PGp, 118±6 and M2 k(d) (pM), WR, 65±12; Egp, 67±6; PGp, 92±2). The inter and intra-species differences found may be related to their respective history of confinement rather than to their history of exposure to high altitude. Copyright (C) 1998 Elsevier Science Inc.