Suramin has been shown to have an effect on bone résorption in in vitro models. It is not clear if a similar effect is seen in patients treated with suramin. The clinical effect of suramin treatment on total serum calcium was examined in two groups of patients with hormone-refractory prostate cancer. In all, 28 patients in group 1 were examined within 2 weeks before and 2 weeks after suramin treatment and 72 patients in group 2 were examined within 2 weeks before, during, and after treatment with suramin. In addition, calcium controls spiked with suramin were run in three different commercially available assays for evaluation of the effect of suramin dose on calcium determination. Group 1 patients showed a decrease in serum calcium after treatment with suramin. The mean uncorrected serum calcium level was 2.29 ±0.025 mmol/1 before treatment and 2.09 ±0.025 mmol/1 after treatment (P < 0.0001, paired Wilcoxon test). The mean serum calcium value corrected for albumin was 2.33 ±0.02 mmol/1 before treatment and 2.24 ±0.02 mmol/1 after treatment (/> = 0.0022, paired Wilcoxon test). Group 2 patients also displayed a decrease in serum calcium after treatment with suramin. The mean baseline value was 2.23 mmol/1 (median 2.26 mmol/1, range 1.20-2.54 mmol/1). The mean level of serum calcium corrected for albumin as determined at the end of treatment was 2.14 mmol/1 (median 2.16 mmol/1, range 0.98-2.46 mmol/1). In all, 48 patients for whom pre- and posttreatment values were available for analysis displayed a median calcium decrease of 0.09 mmol/1 (P = 0.0005, Wilcoxon signed-rank test for the null hypothesis of no change). For 68 patients in group 2, data on serial serum calcium measurements during treatment were available for analysis. A projected median decrease in serum calcium of 0.06 mmol/1 (range -0.43 to 0.72 mmol/1) over an 8-week interval of suramin therapy was found. Overall, 47 of the 68 slopes were negative (P -0.0022, Wilcoxon signed-rank test). Nine patients were treated with suramin for less than 6 weeks. These patients' calcium levels were significantly higher than those of 50 patients treated for longer periods (median value 2.24 versus 2.16 mmol/1, P = 0.035, Wilcoxon rank-sum test). No correlation was found between suramin dose and calcium level using the Kodak Ektachem, Hitachi 914, or Synchron Clinical System CX3 method. In conclusion, suramin treatment was consistently associated with decreases in serum calcium in two groups of patients with hormone-refractory cancer. Suramin placed in calcium controls did not affect calcium determination using three commercially available methods.