4-PIOL is a structural analog of GABA that has low efficacy at GABA(A), receptor Cl^- channels and activates a nondesensitizing Cl^- conductance in central neurons. We investigated the biophysical mechanisms of its low efficacy in embryonic olfactory bulb neurons, which express a limited number of GABA(A) receptor subunit transcripts. Spectral analysis of GABA- and 4- PIOL-induced current fluctuations evoked in whole-cell recordings showed that three components with mean durations of ~0.7, 5, and 50 msec adequately describe the kinetics of the responses induced by both ligands. The contribution of the longest-lasting component was ~60% in the spectra of GABA-evoked responses but <3% in the spectra of 4-PIOL-evoked responses. This is interpreted as a low incidence of long-lasting bursts in 4-PIOL-evoked responses. No difference was evident between the average inferred unitary conductances for 4-PIOL-and GABA-induced channels. These results at the level of the whole cell were confirmed and extended in outside-out single channel recordings. Taken together, the results indicate that the mechanism responsible for the low efficacy of 4-PIOL is the inability to produce frequent bursts of long duration.