Long-term potentiation (LTP) of the hippocampal population spike in area CA1 was studied in the hippocampal slice before, during, and after inhibition of protein synthesis. LTP was tested 15 and 30 min following addition of the protein synthesis inhibitor cycloheximide (CXM) to the bathing medium. Stimulation-induced LTP of the population spike was reduced in slices incubated in CXM for 15 min and completely blocked if incubated for 30 min. Measures of protein synthesis inhibition under the same conditions showed 79% at 15 min and 85% after 30 min. Tests of the effects of repeated LTP treatments at these same time points in the absence of CXM and evaluation of the time course of recovery of LTP from CXM blockade were also conducted. The results confirm previous observations and indicate that a critical amount of protein synthesis inhibition is required to completely block LTP in the hippocampal slice.