The immune defense mechanisms of mucosal surfaces involve secretory immunoglobulin A (sIgA) antibodies and, to a lesser degree, other specific and nonspecific immune factors. These antibodies are dependent on a secretory component (SC) for their transmission through the epithelium. This SC is also secreted without Ig as free SC (FSC). The kidney does produce these proteins; however, the ability of the lower urinary tract to secrete them has not been shown. Thus, an upper urinary tract infection should produce more urinary sIg and possibly more FSC than a lower tract infection. To demonstrate this, urine was obtained from normal controls (N = 33), cystitis patients (N = 22), and pyelonephritis patients (N = 27). Monoclonal antibodies binding to specific conformational epitopes were used in an enzyme-linked immunosorbent assay to detect the levels of sIgA and FSC in these groups. Previous sIgA measurements have been hampered by lack of specificity of the capture antibody. Urine creatinine was obtained to correct for the effect of diuresis. A one-tailed Student's t-test for nonparametric populations was performed to assess differences. The sIgA levels in the normal and cystitis groups were equivalent (1.4 μg/mg/mL and 1.3 μg/mg/mL, respectively; P = 0.32). When these two groups were compared with the pyelonephritis group (24.1 μg/mg/mL), a statistically significant difference was seen (P = 0.012 and P = 0.011, respectively), with no overlap. There was a statistical difference in the levels of FSC in these same groups, but a large degree of overlap. Urinary level of sIgA as measured by this monoclonal antibody is a sensitive test to differentiate pyelonephritis from cystitis, but FSC levels are not predictive. This may be due to differential secretion of sIgA by upper and lower urinary tract mucosa when exposed to infectious agents.