Regardless of a wide research interest the nature of a relationship between cannabis use and schizophrenia is controversial. One of the physiological abnormalities in schizophrenia is attention-modulated deficit in prepulse inhibition (PPI), which is a normal reduction in the startle reflex magnitude when a non-startling stimulus (prepulse) precedes the startling stimulus (pulse). This experiment was designed to determine whether or not otherwise healthy people using cannabis would exhibit attention-modulated deficit in PPI. The startle reflex was recorded in carefully screened healthy humans attending to and ignoring auditory pulse and prepulse stimuli separated by short (20-200 ms) and long prepulse intervals (1600 ms). In contrast to 12 non-using controls, cannabis use in 16 healthy humans was associated with significant reduction in%PPI while attending to auditory stimuli, but not while ignoring them. The PPI was correlated with the duration of cannabis use but not with the concentration of cannabinoid metabolites in urine and the recency of cannabis use in the preceding 24 hours. Cannabis use was not associated with changes in prepulse facilitation of startle reflex magnitude (%PPF) at long prepulse intervals, prepulse facilitation of startle reflex latency and startle reflex magnitude in the absence of prepulses. These results suggest that chronic, but not acute, use of cannabis is associated with schizophrenia-like disruption in PPI in healthy controls. Such reduction in PPI is attention-dependent and does not reflect a global deficit in sensorimotor gating in cannabis users.