The Drosophila protein Rop shows similarity with the Sec1p protein of S. cerevisiae. Sec1p has an essential role in secretion, whereas most related proteins from higher organisms are hypothesized to function in neurotransmitter release. We show that, like the latter proteins, Rop is expressed in the nervous system, but it is expressed in other tissues as well, many of which are actively engaged in secretion. We have isolated mutations in the Rop gene and find that the extracellular accumulation of a number of normally secreted cellular products fails to occur in null mutant animals, which subsequently die at a late embryonic stage. Electrophysiological recordings on temperature-sensitive Rop mutants show that reductions in Rop activity result in a loss of the normal synaptic response to a light stimulus. These data suggest that a member of the Sec1p class of proteins has an in vivo function in both general secretion and synaptic transmission.