BACKGROUND Total cysteine (tCys) in plasma has recently been linked to cardiovascular risk and is also associated with cardiovascular risk factors, including body mass index (BMI) and cholesterol. Changes and predictors of change in tCys concentrations over a mean follow-up time of 6.0 (5.2-7.2) years were assessed in this study. METHODS Baseline data from the Hordaland Homocysteine Study recorded in 1992-1993 included tCys, total homocysteine (tHcy), and various lifestyle and cardiovascular risk factors. In 1998-1999, the same measurements were repeated in 3,732 individuals born in 1950-1951 and 3,339 individuals born in 1925-1927. Most of the statistical analyses were done separately in the four age and sex groups. RESULTS The overall mean values of tCys were higher at follow-up [mean (SD), 296 (41) micro mol/L] than at baseline [278 (36.5) micro mol/L]; P <0.0001. The mean percentage of increase in tCys in the different age and sex groups ranged from 4.9% to 8.5%. There was a significant correlation between the tCys values measured on the two occasions (Spearman correlation coefficient, 0.55-0.59 in the different age and sex groups; P <0.0001). The change in tCys correlated with changes in BMI, cholesterol, and diastolic blood pressure in the younger age group, whereas only changes in BMI predicted changes in tCys in the older age group. CONCLUSIONS tCys increased in the 6 years between the two measurements. Factors related to the baseline tCys values, including BMI and the change in BMI, predicted the tCys changes over time.