The usefulness of measuring serum antibodies to Tamm-Horsfall protein (THP) for diagnosing the level of acute urinary tract infections in adult women was evaluated. There was a significant (p<0.001) elevation of IgG and IgA anti-THP in pregnant and non-pregnant women with acute pyelonephritis compared to women with acute cystitis. The changes in anti-THP antibody titre among patients with acute pyelonephritis varied considerably, limiting the value of determining such antibodies for diagnostic purposes. Patients with febrile infections of non-renal origin demonstrated an antibody response comparable to the pyelonephritis patients. One explanation for these results could be that fever is associated with transient renal tubular damage, thus exposing THP to the immune system. Polyclonal antibody activation seems less likely since neither an IgM antibody response to THP, nor an increase in antibody titre to poliovirus could be demonstrated.