Few cases of nephrolithiasis (renal calculi) have been reported in bottlenose dolphins Tursiops truncatus. A case-control study was conducted to compare ultrasonographic images and clinicopathologic serum and urine values among 14 dolphins with nephrolithiasis (mild cases: 1 to 19 nephroliths, n = 8; advanced cases: > or = 20 nephroliths, n = 6) to 6 controls over an 18 mo period. Archived nephroliths collected postmortem from 7 additional bottlenose dolphins were characterized using quantitative analysis. All advanced cases had bilateral nephroliths, and 67% had visible collecting ducts. During the study, 2 of the advanced cases developed hydronephrosis, and 1 of these cases had ureteral obstruction due to a nephrolith. Compared to controls, cases (mild and advanced) were significantly more likely to have anemia (hematocrit [HCT] < 38%), high blood urea nitrogen (>59 mg dl(-1)), high creatinine (>1.9 mg dl(-1)), and low estimated glomerular filtration rate (<150 ml min(-1) 2.78 m(-2)). Advanced-case urine samples were more likely to have erythrocytes, occult blood, and lower pH compared to mild cases and controls. Mean serum uric acid among all study groups was low (0.15 to 0.27 mg dl(-1)). Urinary uric acid concentrations were highest among mild cases (272 mg g(-1) creatinine), but advanced cases had levels lower than that of controls (40 and 127 mg g(-1) creatinine, respectively). All nephroliths were characterized as 100% ammonium acid urate. We conclude that nephrolithiasis is clinically relevant in dolphins and can decrease renal function and HCT. The presence of nephrolithiasis, presumably ammonium acid urate nephrolithiasis, in the face of low serum uric and relatively low urinary uric acid in advanced cases may indicate a metabolic syndrome similar to that reported in humans.