Accelerated renal cyst development in deconditioned germ-free rats. The influence of environment on renal cyst growth was assessed in experiments utilizing 56 germ-free and 32 conventional male Sprague–Dawley rats fed 2% nordihydroguaiaretic acid (NDGA). Among three groups of six germ-free rats allowed ad lib intake of NDGA for six weeks and deconditioned (placed into the ambient laboratory environment) at the start, at the midpoint, or not at all, cyst formation and interstitial changes (both severe) were noted only among animals deconditioned at the midpoint. Among 14 germ–free rats that were offered 0.4 g NDGA daily, deconditioned after two weeks, and sacrificed 0 to 15 days thereafter, nephron dilation and thymidine uptake by renal tubular epithelium appeared within one to three days and correlated in magnitude with each other and with the duration of the contamination interval. Deconditioning, a prior period of four or more days of exposure to NDGA in the germ-free state, the duration of the contamination period, and the presence of cecal flora were identified as prerequisites to accelerated cyst formation in this model, while the dose of ingested NDGA, the presence of bacteria within the kidney, an action of bacteria on NDGA within the colon, and the type(s) of organisms colonizing the host were not. These findings provide experimental evidence that environmental circumstance can modulate the expression of renal cystic disease.