Infection with Helicobacter pylori increases the risk for gastric non-Hodgkin's lymphoma (GNHL). Strains that express CagA protein are thought to be particularly virulent. It was determined whether CagA+ H. pylori infection increased the risk for GNHL more than CagA infection. Thirty-two cases and 130 controls previously tested for H. pylori antibodies were tested for CagA antibodies by ELISA. The risk for GNHL was compared among CagA+, CagA-, and uninfected persons by use of conditional logistic regression. CagA+ subjects had 8.2 times the risk for GNHL than uninfected persons (95% confidence interval [CI], 2.5-26.7). CagA- subjects had 4.4 times the risk for GNHL than uninfected persons (95% CI, 1.2-16.5). Among infected subjects only, CagA+ infection was not associated with significantly increased risk for GNHL when compared with CagA- infection (odds ratio, 2.1; 95% CI, 0.8-5.4). This study does not support a major role for CagA in lymphomagenesis.