Pyelitis with acute and chronic pyelonephritis and also primary chronic pyelitis were easily initiated in female rats by a single non-traumatic retrograde infusion of bacteria into the urinary tract. The virulence of the bacterial species and the time of observation were related to the type and extent of lesions, but pyelitis regardless of the virulence appeared to be an important factor. The apex and fornix of the renal pelvic lumen were anatomic sites of persistent pyelitis which permitted local proliferation of bacteria for long periods. Cortical and medullary lesions were anatomically related to these areas of underlying pyelitis. Spread of infection followed a pattern of contiguity rather than ascending tubular infection. The experimental model has many of the features of chronic urinary infections in man and suggests that pyelitis is an important factor in the pathogenesis of chronic pyelonephritis initiated by retrograde infection.