A survey is presented of recent experiments which utilize spontaneous neuronal spike trains as dependent and/or independent variables in developing cerebral cortex cultures when synaptic transmission is interfered with for varying periods of time. Special attention is given to current difficulties in selecting suitable preparations for carrying out biologically relevant developmental studies, and in applying spike-train analysis methods with sufficient resolution to detect activity-dependent age and treatment effects. A hierarchy of synchronized nested burst discharges which approximate early slow-wave sleep patterns in the intact organism is established as a stable basis for isolated cortex function. The complexity of reported long- and short-term homeostatic responses to experimental interference with synaptic transmission is reviewed, and the crucial role played by intrinsically generated bioelectric activity in the maturation of cortical networks is emphasized.