We measured the effects of Tamm-Horsfall glycoprotein (THP) on calcium oxalate monohydrate (COM) crystal aggregation (Ac) in vitro as well as intrinsic viscosities (Vi) of THP at pH 5.7 and 200 mM NaCl and studied the effects of calcium and citrate on these parameters. THP were isolated from 24-h urines of seven male recurrent calcium stone formers (RCSF) and eight age-matched male healthy volunteers (N, normal). At basal conditions, RCSF-THP inhibited Ac by 28 +/- 10% and normal THP by 60 +/- 6% (P = 0.028). In the presence of calcium, increasing THP concentrations from 16 to 28 and 40 mg/l progressively lowered inhibition by RCSF-THP, but not by N-THP. At 40 mg/l, inhibition by N-THP was 27 +/- 9% vs. -43 +/- 8% by RCSF-THP (P = 0.001), i.e., all stone former THP promoted Ac. With an additional 3.5 mM of citrate, inhibition of Ac was 56 +/- 5% by normal and 34 +/- 6% by stone former THP (P = 0.021), and all seven stone former THP again inhibited Ac. Vi of RCSF-THP was higher than that of N at basal conditions (162 +/- 21 vs. 93 +/- 15 ml/g, P = 0.021) and in the presence of 5 mM calcium (352 +/- 54 vs. 118 +/- 17 ml/g, P = 0.001), i.e., RCSF-THP were more self-aggregated, but not when citrate was added (185 +/- 29 vs. 123 +/- 19 ml/g). (ABSTRACT TRUNCATED AT 250 WORDS)