Ageing affects feline lymphocyte homeostasis in a similar pattern to that observed in other long-lived mammalian species, contributing to increased levels of morbidity and mortality in the ageing cat. Insulin-like growth factor-I (IGF-I) is now recognised as an important endocrine regulator of immunity and has been shown to decline with age in humans and rodent species. Analysis of plasma IGF-I in adult and senior cats confirmed that the older cats had significantly lower circulating levels of IGF-I. In order to determine whether an association existed between lymphocyte subpopulations and IGF-I levels in the cat, each parameter was measured and subjected to regression analysis. A highly significant association was found in vivo between plasma IGF-I and CD4(+) T-cell values in the senior group, but no such association was observed in the adult group. In order that this relationship could be examined further, in vitro studies were undertaken to investigate the effects of physiologically relevant concentrations of recombinant human IGF-I (rhIGF-I) on peripheral blood lymphocyte (PBL) cultures from adult and senior cats. While rhIGF-I induced low-level thymidine incorporation in the lymphocytes isolated from the senior group, it did not enhance the proliferative response to T-cell mitogens, Con A and PHA in either group, nor did it rescue cells from oxidatively induced apoptosis. Furthermore. the proliferative response of PBL from seniors did not attain the magnitude of that from the adults at any concentration of rhIGF-I. We propose that the observed association is not a direct effect of IGF-I on PBL, but may be mediated through an effect of IGF-I on the thymus. (C) 2004 Elsevier Ireland Ltd. All rights reserved.