Spontaneous echo contrast (SEC) of the left atrium is associated with increased risk of thromboembolism in patients with mitral stenosis (MS). The determination of the presence and severity of left atrial (LA) SEC is of prognostic importance in these patients. Harmonic imaging (HI), a novel echocardiographic technique that differs from conventional fundamental imaging (FI) in that it involves transmitting ultrasound at one frequency and receiving at twice the transmitted frequency, produces better endocardial border definition and myocardial opacification. However, there are no data about its value for the detection of LA SEC. The purpose of this study was to investigate the utility of transthoracic noncontrast tissue HI in the detection of LA SEC in patients with MS. Seventy-four consecutive patients with MS (49 women, mean age 51 years) underwent standard transthoracic echocardiography (TTE) in both HI and FI modes and transesophageal echocardiography (TEE) to determine the presence and severity of LA SEC. Left atrial SEC was graded by TEE as either mild (only seen at high gain) or severe (visible in the entire left atrium at normal gain control of the equipment). The control group comprised 30 patients randomly selected from patients who did not have LA SEC at the TEE examination. Atrial fibrillation was found in 46 patients (62.2%). The mean mitral valve area and mean mitral gradient were 1.0+/-0.3 cm(2) and 8.2+/-4.1 mm Hg, respectively. Nine patients (12.2%) had episodes of systemic embolism; 8 had stroke, and 1 had peripheral embolism. Left atrial thrombus was found in 11 patients (14.9%) by TEE. Left atrial SEC was present in all but one patient by TEE (mild in 35 patients, severe in 38). Fundamental imaging with TTE, however, revealed LA SEC in only 5 (6.8%) of the 73 patients. In contrast, with HI, LA SEC could be detected in 63 (86.3%) patients. In the detection of severe LA SEC, the sensitivities of FI and HI were 13.2% (5/38) and 100% (38/38), respectively. Left atrial SEC was not observed in control subjects by either FI or HI. Transthoracic HI significantly enhances the detection of LA SEC in patients with MS.