Serum 1,25(OH)2D and factors related to its production were studied in 39 patients with various degrees of renal insufficiency. Serum 1,25(OH)2D levels correlated positively with 1/serum creatinine values (r = 0.54, P less than 0.001) and negatively with serum phosphorus (r = -0.39, P less than 0.02) and age (r = -0.33, P less than 0.05). There was no significant correlation between 1,25(OH)2D levels and serum calcium or calcitonin or PTH, although the logarithm of PTH correlated inversely with 1,25(OH)2D levels (r = -0.47, P less than 0.01). Patients who had normal or supranormal 1,25(OH)2D levels despite low GFR tended to have low serum phosphorus values. Serum levels of bone Gla protein (BGP), a biochemical marker for bone metabolism, correlated negatively with 1/serum creatinine (r = -0.39, P less than 0.02) and positively with PTH (r = 0.57, P less than 0.001) and age (r = 0.33, P less than 0.05). Prophylaxis with 1,25(OH)2D should be considered in patients with significantly decreased serum 1,25(OH)2D levels, as seem to occur when serum creatinine is greater than 4.0 mg/dl. However, despite the statistically significant correlation between serum 1,25(OH)2D and 1/serum creatinine, direct measurement should be used to ascertain the serum concentration of 1,25(OH)2D in chronic renal insufficiency.