The pneumococcus is a leading cause of serious bacterial infection worldwide. Given the difficulties with available assays for the diagnosis of invasive nonmeningitic pneumococcal infection, we evaluated monovalent slide latex agglutination reagents among patients with blood culture-confirmed pneumococcal infection and control patients in Baltimore, Maryland, USA; São Paulo, Brazil; and Cairo, Egypt. Among 50 patients with invasive nonmeningitic pneumococcal infection, 23 had a positive urine test for a sensitivity of 46% (95% confidence intervals of 32% and 61%). Among 39 healthy children, 36 had a negative assay, for a specificity of 92% (95% confidence intervals of 78% and 98%). Among 80 children with pneumonia without a positive blood culture for Streptococcus pneumoniae, the specificity was 88% (95% confidence intervals of 78% and 94%). Although the assay was fairly specific, the positive predictive value using optimistic assumptions was only 73%-83%. This study suggests that this assay has a sensitivity and positive predictive value that may limit its value in some settings.