Although organophosphate (OP) insecticides have been recognized as having neuropathic potential, a relationship with Guillain-Barre syndrome (GBS) has not been previously confirmed. A cluster of 7 cases of GBS was noted over an 11-yr period in an isolated farming region in the Northern Cape Province of South Africa, an area subject to intensive aerial application of OP insecticides. Observed cases were more than 4 times higher than expected based on a Poisson probability distribution. Four cases were clustered in an area where the topography showed a marked hollow, and where spray drift of aerial OP insecticides was anticipated. The rate of GBS in this subcluster was more than 14 times higher than expected. The authors explored the hypothesis that aerial OP insecticide application was related to the raised incidence of GBS in this area and made suggestions for future research.