We describe a versatile NMR probe that is designed for a variety of in vivo spectroscopic studies on small animals in vertical wide-bore magnets. Replaceable brackets enable the coils to be exchanged readily in order to observe 1H, 13C, 31P, and other nuclei, and to carry out double-resonance experiments. Two solenoidal coil designs are described and applied to observe 31P, 13C, and 1H natural abundance spectra of subcutaneously implanted human tumors in mice. For 31P and 31C observation with 1H decoupling, a concentric coil arrangement was employed with a broadband inner coil and the outer coil tuned to 1H at 400 MHz. A single coil tuned to 400 MHz was used to observe 1H resonances. A thin copper foil design was found to be superior with respect to S/N and resolution to previously described Faraday shields used to shield the NMR signals originating from nontumor tissues. 31P spectra of in vivo tumor tissue were compared to spectra of in vitro perfused tumor cells of the same origin. Tumor tissue in vivo exhibited much higher levels of inorganic phosphate and phosphocreatine. Signals from [13C2]glucose and its major metabolite, [13C2]lactate, were readily observed and monitored in an unobstructed region of the 13C spectra of tumor tissue in vivo following the injection of [13C2]glucose in adjacent tissues. A 1H spectrum of tumor tissue, characterized by five broad resonances, was observed with excellent water suppression.