The adaptive responses to sucrose and fat diets were investigated in two species of spiny mice, Acomys russatus and Acomys cahirinus, in relation to their propensity to develop diabetic-like symptoms. A russatus gained weight pronouncedly, both on regular and fat-rich seed diet, did not exhibit hyperglycemia or hyperlipidemia but had highly increased hepatic triglyceride content in association with high levels of circulating free fatty acids and incidence of ketonuria in 10 of 41 animals. On the other hand, A. cahirinus exhibited a moderate weight gain on the fat diet which was accompanied by hyperglycemia but no hyperlipidemia or ketonuria. Neither weight gain nor ketonuria were evident in A. russatus and A. cahirinus on the sucrose-rich diet, but there was hyperlipidemia in the latter species. A. cahirinus, in particular, showed many-fold induction of liver enzymes, of regulatory importance in the pathways of glycolysis and lipogenesis, which could be linked to the hyperlipidemia in this species. On the fat diet there was a smaller increase in activity in enzymes related to gluconeogenesis in A. russatus compared with A. cahirinus, as well as a smaller suppression of glycolytic and lipogenic enzymes. Adipose tissue lipoprotein lipase activity rose in response to the fat-rich diet, more markedly in A. russatus than A. cahirinus in correlation to the more marked weight gain and hyperinsulinemia in this species. The affluent diets, especially sucrose, elicited an increase in circulating triiodothyronine levels which was more pronounced in A. cahirinus than in A. russatus.(ABSTRACT TRUNCATED AT 250 WORDS)