The insulin-like growth factor (IGF) axis may play opposing roles in health and disease. The age-related declines in growth hormone and IGF-I may be associated with potentially deleterious changes in body composition and functioning, but recent studies suggest that IGF-I levels may be related to risk of prostate, colorectal, premenopausal breast, and possibly other cancers. Thus, we studied dietary influences on plasma IGF-I and IGF-I:IGF-binding protein-3 ratio in 753 men in the Health Professionals Follow-Up Study who completed a food frequency questionnaire. In this generally well-nourished population of middle-aged to elderly men, plasma IGF-I and IGF-I:IGF-binding protein-3 molar ratio tended to increase with higher intake of protein and minerals, including potassium, zinc, magnesium, calcium, and phosphorus. Men with relatively high intakes of total protein (top quintile) and minerals (top quintile of the five minerals combined) had a 25% higher mean plasma level of IGF-I compared with those in the low quintiles simultaneously. The major sources of animal protein, including milk, fish, and poultry, but not red meat, as well as total vegetable protein, were associated with an increase in IGF-I levels. Energy intake was positively related to plasma IGF-I level but only in men with body mass index <25 kg/m(2). The age-related decline in plasma IGF-I may be exacerbated by low intakes of protein and minerals. The potential role of these dietary factors on cancer risk through altering IGF-I levels requires study.