The biophysics of block of NMDA receptor channels has been investigated extensively during the past 8 years. In the last few years, cloned NMDA receptor channels have become available. Here we have discussed advantages and disadvantages of studying block phenomena in cloned NMDA receptors. Some recent work on the pore block of the cloned NMDA receptor channels was critically reviewed and extended by data about the calcium block. Novel effects of kainate on cloned NMDA receptors and of NMDA on cloned AMPA receptors were reported and discussed with respect to recent work concerning possible occurrence of NMDA-AMPA hybrid channels.