Weight gain through middle age is a common phenomenon that increases the risk for different types of metabolic diseases and functional limitations later in life. This study examined genetic and environmental influences on the evolution of body mass index (BMI) in women from middle to old age. BMI was evaluated in 102 monozygotic and 114 dizygotic pairs of twin sisters from the year 1975, when they were 42.6 +/- 3.4 years-old, and thereafter in 1981, 1990, 2001 and 2004, in a total 29-year follow-up period. We examined genetic and environmental influences explaining BMI overall level and its rate of change using a latent growth modeling approach. The results showed that mean (+/-SD) BMI increased from 24.1 +/- 3.1 to 28.2 +/- 5.1 kg/m(2) during the 29-year period. The heritability of BMI showed a consistent increment across occasions, from 54% in 1975, to 72% in 2004. Genetic influences accounted for both overall BMI level (60%) and BMI rate of change (64%). Genetic and environmental correlations between BMI level and rate of change were: r(g) = 0.40 and r(e) = -0.24, respectively. We conclude that in relatively healthy women, genes affecting level of BMI may differ from those affecting change in BMI with age. These results provide a basis for identifying genetic variants for change in BMI.