Abstract A radioisotope dilution technique for measurement of inorganic pyrophosphate (PPi) in synovial fluid is described. Its precision based on duplicate measurements is ±4 μg per 100 ml. PPi levels in 20 of 23 joint fluids from patients with arthritis other than pseudogout clustered about a mean ± S.D. of 22 ± 6.3; 3 control fluids showed elevated values. Of 18 joint fluids from patients with calcium pyrophosphate crystal deposition disease (pseudogout), 15 showed inorganic PPi levels that were greater than 2 S.D. from the control mean, 2 were borderline, and one fell in the normal range. The mean ± S.D. of the group was 100.4 ± 93. Inorganic orthophosphate, total and ionized calcium, alkaline phosphomonoesterase activity against both p-nitrophenylphosphate and β-glycerophosphate, and alkaline phosphomonoesterase isozymes were not significantly different in joint fluids from control and pseudogout patients. Preliminary studies on the solubility of calcium pyrophosphate dihydrate miscocrystals in various solvents such as distilled water, Tris buffer, dialyzed and anaerobically processed fresh joint fluid and plasma are presented. The levels of PPi attained were of the same order of magnitude as those found in joint fluids from pseudogout patients. Magnesium ions and protein increased solubility; calcium and orthophosphate ions decreased it. Whether or not the PPi levels found in pseudogout fluid represent saturation levels in vivo cannot be answered from the present data.