1. Kindling is an animal model of epilepsy in which repeated administration of a subconvulsant stimulus, electrical or chemical, produces a gradually increasing electroencephalographic and behavioral response which culminates in a behavioral seizure. 2. The biological basis of the kindling effect remains unknown but alterations in neurotransmission figure prominently in most hypotheses. Several factors of kindling are considered as central to the phenomenon. It is most important to recognize that the development of kindling and a kindled seizure are not necessarily the same phenomenon. 3. Kindling is essentially a permanent change in the sensitivity of the brain to a stimulus. It therefore follows that the biological basis for kindling must be a permanent change. Permanent changes in neurotransmitter levels or receptor parameters have not been conclusively demonstrated in kindling. Other possible permanent changes include changes in Ca activated mechanisms which alter neuronal structures such as dendritic spines. 4. An essential component to the riddle of kindling is the absolute requirement for an inter-stimulus interval of at least 1–2 hours. This suggests that the biological process which leads to kindling occurs in this critical period. Recent experiments with cysteamine suggest that the events in this critical period can be manipulated chemically. An understanding of these events will help to clarify the biological basis of kindling. |