Unsaturated plasma transcobalamin II (UTC II) and cobalamin were measured in two selected age-groups of like-sexed mono- and dizygotic twins. For UTC II, a higher mean level was found in women than in men, and in the older (57 to 61 years) than in the younger (33 to 39 years) age group. Testing of genetic-environmental models revealed that variation in plasma levels of UTC II is almost exclusively genetically determined. More than 50% of the variation in cobalamin levels was accounted for by genes, the remainder being due to person-specific environmental factors (for older males no model gave a good fit). A negative correlation was noted between UTC II and cobalamin levels. The correlation coefficient was low, and the variation in UTC II accounted for only about 4% of the variation in the cobalamin level. This finding suggests that a pathologically high value of one of the variables may have clinical significance, regardless of the value of the other variable. For 22 patients studied longitudinally, a clear tendency to maintain plasma levels at constant levels over long periods of time was found, suggesting that certain degrees of deviation from these levels may have clinical relevance.