Hypocalcemia is a common finding in TSS. This has been causally related to the hypoalbuminemia of TSS. To more clearly define the mechanism responsible for this hypocalcemia, we examined the serum concentrations of CaT, Ca+ +, iCT, albumin, and DBP in 28 women meeting the case-study definition of TSS. Mean CaT was 2.18 +/- 0.36 mM/L (S.D.), Ca+ + was 0.93 +/- 0.19 mM/L, and iCT was 1941 +/- 978 pg/ml; all were significantly different (p less than 0.01) from the normal values of CaT (2.38 +/- 0.09), Ca+ + (1.09 +/- 0.04) and iCT (less than 30 to 135). A significant inverse correlation was found between iCT and both CaT and Ca+ +, p less than 0.001. Serial values were measured in two women in whom the iCT values declined each day. Gel filtration of the iCT from two patients with the highest values suggested that some polymeric molecular species, rather than authentic CT, accounted for 90% of the circulating iCT value. No abnormalities of DBP levels were found, and no correlation with CaT, Ca+ +, or iCT was evident. The hypocalcemia of the TSS represents a reduction in both CaT and Ca+ + concentrations, which may be at least partially accounted for by the elevated iCT concentrations.