Insulin resistance is of pathogenetic importance for the development of non-insulin-dependent diabetes mellitus (NIDDM). However, not much is known about the variation in insulin sensitivity in the individual over longer periods. Consequently, we measured insulin sensitivity (Si) and glucose effectiveness (Sg) in healthy young men (N = 10) 5 times over a period of 15 months using a frequently sampled intravenous glucose tolerance test (FSIVGTT) with minimal-model analysis (study of seasonality). The maximal aerobic capacity (V(O2)max), fat-free mass, body mass index (BMI), and 24-hour ambulatory blood pressure (BP) were also assessed. Furthermore, we performed a study designed to evaluate the day-to-day variation in Si and Sg (study of day-to-day variation). Here, we studied Si and Sg in healthy young men (n = 8) within 2 weeks. In the study of seasonality, the coefficient of variation (CV) for Si was 24.0%, whereas the CV for Sg was 26.0%. Anticipating a seasonal variation in Si following a sine curve with a cycle length of 1 year and an unknown phase and amplitude, we tested this hypothesis with a multiple linear regression model that allows for different levels of Si between individuals, and failed to detect any impact due to this. Si (mean +/- SD, 1.17 +/- 0.28 x 10(-4) x min(-1) x pmol/L(-1), P = .38), Sg (0.023 +/- 0.006 min(-1), P= .71), fasting insulin (21.2 +/- 7.3 pmol/L, P= .98), V(O2)max (3.8 +/- 0.6 L/min, P= .13), and fat-free mass (64.9 +/- 2.5 kg, P = .92) were constant over time. In the study of day-to-day variation, we found a CV for Si of 17.3% and a CV for Sg of 23.3%. In conclusion, we found that the variations in Si and Sg were slightly higher than those found in studies performed to establish the day-to-day variation. However, no significant seasonal variation in Si and Sg was evident in this group of healthy young lean caucasian men. Consequently, indices of Si and Sg obtained at different times of the year appear comparable.