Our goal was to assess the utility of manganese dipyridoxyl diphosphate (MnDPDP) as a negative hepatic contrast agent in short inversion time IR MRI (STIR). Twenty patients with focal liver lesions (15 with metastatic disease, 5 with hemangiomas) underwent MRI (T1-weighted SE, breath-hold GE, and STIR sequences) before and after infusion of MnDPDP (5 mumol/kg). We then compared the results obtained with each sequence for hepatic parenchymal enhancement, lesion-to-liver contrast-to-noise ratio (C/N) measurements, and the number of focal liver lesions observed in pre- and postcontrast images. Hepatic enhancement values of 25.3 +/- 9.7 and 33.6 +/- 2.7% (mean +/- SEM) were obtained for the T1-weighted SE and GE sequences, respectively. The STIR sequence showed 78.9 +/- 2.1% negative enhancement (decrease of parenchymal signal intensity). Although a significant (p < 0.0001) C/N increase was seen after MnDPDP administration for all sequences, STIR showed the highest increase (149.0 +/- 25.5%) compared with T1-weighted SE (58.5 +/- 12.7%) and GE (83.3 +/- 7.2%) sequences. Similarly, more lesions for all sequences were detected, but again STIR showed the greatest postcontrast increase (29.0%). MnDPDP is an effective hepatic contrast agent. As both the negative hepatic enhancement and the increase in lesion-to-liver C/N were superior with the STIR sequence when compared with the positive enhancement and C/N values produced by the T1-weighted sequences, it should be considered for inclusion in the imaging protocol for patients with focal liver disease.