The clinical evaluation of nine patients with severe infant botulism revealed an identifiable progression of signs due to blockade of the cholinergic synapse similar to that described for competitive blocking agents. This predictable sequence reflects different "margins of safety" for muscles involved in repetitive activities, diaphragmatic function and movement of the extremities. It is important for the clinician to realize that return of peripheral motor activity does not signify a completely recovered cholinergic synapse. Instead of having a four- to five-fold margin of safety, the infant remains close to the point of neuromuscular blockade. Added insults or stress to neuromuscular transmission may precipitate respiratory failure. An understanding of the signs associated with progressive impairment of cholinergic synapses both during onset and during resolution of disease will allow safe care of the infant and will diminish the risk of iatrogenic complications. Evaluation of head control is the most sensitive physical finding indicative of return of adequate neuromuscular function and signifies that oral feedings can be reinstituted.