The aminoglycoside antibiotics neomycin and streptomycin were tested on the synaptic activity of the CA1 pyramidal neuron-Schaffer collateral interconnections in rat hippocampal slices. 2. Neomycin (0.5 mM) decreased the magnitude and shifted to the right the stimulus-response curve of the somatic and dendritic excitatory postsynaptic potential (EPSP) and the somatic population spike (PS). 3. Streptomycin (1 mM) decreased the magnitude and shifted to the right the stimulus-response curve of the somatic and dendritic EPSP and the somatic PS. 4. High (+2 mM) calcium solutions were able to prevent the effects induced by the antibiotics and to shift to the left the stimulus-response curve of the 0.5 mM neomycin and 1 mM streptomycin treated hippocampal slices. 5. The data demonstrate an effect of aminoglycoside antibiotics on a central mammalian hippocampal synapses, that may depend on an interference of the drugs on calcium conductances.