Using two different experimental techniques, Tamm-Horsfall mucoprotein (THM) has been reported both to inhibit and to promote calcium oxalate (CaOx) crystallization in ultrafiltered human urine. In this study, these two techniques were used to compare the effects of THM on CaOx crystallization in the same ultrafiltered urine samples. Urine was collected from 10 healthy men and ultrafiltered (10,000 Da). Each sample was divided and to one half was added sufficient human THM to give a final concentration of 35 mg/L. CaOx crystallization was induced in the samples by addition of an oxalate load and by evaporation. Using the evaporation technique THM significantly increased the deposition of CaOx determined as 14C-oxalate, from 9,772 cpm to 43,652 cpm (P less than 0.01). Using the oxalate load method THM had no effect on the metastable limits of the urine with respect to CaOx, and significantly increased the volume of particulate material deposited from 26,000 to 39,995 microns 3/microliters - an increase of 54%. This increase was reduced to 21% when values were corrected for the volume of THM particles recorded in control samples to which no oxalate load was added. Using 14C-oxalate, it was shown that this increase in volume could not be attributed to an enhanced deposition of crystalline CaOx, but was probably the result of an increased polymerization of THM in the presence of CaOx crystals. Despite this, the average size of the particles precipitated in the presence of THM (6.5 microns) was significantly (P less than 0.01) less than that observed in the absence of THM (12.1 microns). It was concluded that the effect of THM on CaOx crystallization in urine depends upon the methodology used to assess it and that promotion would only be expected in vivo in cases of extreme dehydration. Under usual physiological conditions THM would be expected to inhibit CaOx crystal aggregation and to have little effect, if any, on the amount of crystalline material deposited.