The diagnostic and prognostic implications of transient isolated negative T waves were studied in 127 patients in whom acute myocardial infarction (AMI) was suspected. Eight-four patients with no AMI and no electrocardiographic changes served as the control group. The 2 groups were well matched. Twenty-nine patients (23%) with isolated negative T wave had a significant increase in serum creatine kinase (CK)-MB levels and fulfilled the diagnostic criteria for AMI. The increase in serum CK-MB levels did not predict a higher risk of hospital mortality, but during follow-up (median 31 months), a serum CK-MB level above 30 U/liter identified patients with a significantly increased risk of dying (p less than 0.05). Both the number of affected electrocardiographic leads and the sum of negative T-wave amplitudes were significantly related to the follow-up mortality rate (p less than 0.01). The comparison between control subjects and patients with negative T waves during follow-up showed more events among the patients: AMI (17% vs 8%, p less than 0.02); death (24% vs 12%, p less than 0.01); and AMI or death (31% vs 19%, p less than 0.01). Thus, only 25% of patients with aggravated chest pain and isolated negative T waves have AMI. However, the long-term prognosis for the entire group of patients with isolated negative T waves is poor, and any therapeutic intervention should be initiated immediately.