This study describes 56 infants who presented to the Emergency Department of The Children's Hospital of Denver during a 1-year period with an episode of excessive, prolonged crying, without fever and without a cause that was apparent to the parents. The final diagnoses included a broad array of conditions, of which 61% were considered serious. The history provided clues to the final diagnosis in 20% of cases. Physical examination revealed the final diagnosis in 41% and provided clues to the diagnosis in another 13%. Accurate diagnosis requires a thorough physical examination, which should include careful skin inspection underneath all clothing, palpation of all large bones, fluorescein staining of the cornea, eversion of eyelids, rectal examination, retinal examination, and thorough neurologic examination. "Screening" laboratory tests, except for urinalysis and urine culture, were of little help. This study indicates that for those patients in whom the physical examination is not diagnostic, the persistence of excessive crying after the initial examination predicts the presence of a serious cause. Those infants who cease crying before or during the initial assessment are unlikely to have a serious cause. Recommendations for a stepwise assessment are offered.