Clinical investigations of infants hospitalized with botulism demonstrate a remarkable uniformity of complaints and physical findings. Constipation precedes a course of progressive weakness and cranial nerve dysfunction. Examination reveals hypotonia, hyporeflexia, and a variable pattern of involvement of the motor cranial nerves. Initial laboratory investigations should include electrodiagnostic tests, because findings of an incremental response to rapid, repetitive nerve stimulation and of brief, small-amplitude motor units on electromyography are virtually pathognomonic of botulism in the infant. Differential diagnosis includes disorders that may produce generalized depression of the central nervous system, such as septicemia, meningitis, metabolic disturbances, and intoxications. Specific involvement of the neuromuscular system includes acute polyneuropathies, diseases of the anterior horn cell, congenital myopathies or muscular dystrophy, and neonatal myasthenia gravis. Recent studies have expanded the clinical spectrum of infant botulism to include some cases of sudden infant death syndrome and otherwise nonspecific constipation.