The etiology of arthritis episodes in normouricemic patients with gout is still unclear. We propose that the fluctuation in synovial urate level, as well as pH, ion strength, albumin, and globulin values relative to serum levels, could be involved in crystal formation. To assess serum-synovial gradient (SSG), the sera and synovial fluid (SF) of six normouricemic patients (men, age 48-79) with a history of gout (American College of Rheumatology criteria) and acute knee effusion were screened for uric acid, pH, osmolality (Osm), P/Ca, albumin, globulin, and SSG. Monosodium urate monohydrate (MSUM) crystals were determined by polarized light (PL). Infectious arthritis was ruled out via Gram staining and synovial fluid culture. Negative X-ray and PL microscopy results excluded chondrocalcinosis. Five patients (1-5) had inflammatory knee effusion (WBC >2,000/mm(3)), and one (patient 6) had noninflammatory knee effusion (600 WBC/mm(3)). MSUM crystals were found in the WBC of patient 1 only. He had tophaceous gout with normal serum uric acid levels and showed significant negative Osm and P and positive Ca SSG. Two crystal negative patients had severe negative pH SSG with alkaline synovial fluid, significant P/Ca SSG, and high positive globulin SSG, while one of them had supersaturated SF uric acid content. The other patients displayed an increased Osm and P/Ca SSG. All SSG values were five to ten times higher than the coefficient of variance for used methods. Noninflammatory SF of patient 6 does not appear to be related to active gout. The data on SSG for MSUM, pH, Osm, Alb/Glob, and P/Ca in normouricemic patients with gout history and acute knee effusion was not homogeneous. We propose that acid-base and ionic-protein gradient may lead to instability of subsaturated urate solution, thereby predisposing to MSUM deposits within synovial membrane and inducing inflammation.