The effects of perivascular nerve stimulation and phenylephrine on osmolyte release were studied in the intact perfused rat liver and isolated liver parenchymal cells (PC) and nonparenchymal cells. In the perfused liver, electrical stimulation of perivascular nerves (20 Hz/2 ms/20 V) led to a phentolamine‐sensitive increase of cell hydration by 6.5% ± 1.2% (n = 3) and a transient phentolamine‐sensitive stimulation of taurine and inositol, but not betaine, release. These nerve effects were mimicked by phenylephrine, but not prostaglandin F_2α, and were not affected by sodium nitroprusside (SNP) or ibuprofen. Nerve stimulation–induced taurine, but not inositol, release was inhibited by 4,4′‐di‐isothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS) (50 μmol/L). Single‐cell fluorescence studies with isolated liver PC, Kupffer cells (KC), sinusoidal endothelial cells (SEC), and hepatic stellate cells (HSC) revealed that phenylephrine induced an increase in cytosolic free Ca²⁺ only in PC and HSC, but not in KC and SEC, whereas extracellular uridine triphosphate (UTP) produced Ca²⁺ transients/oscillations in all liver cell types studied. Phenylephrine had no effect on osmolyte release from isolated KC and SEC, but increased taurine (but not inositol) release from PC and inositol (but not taurine) efflux from HSC. The data suggest that: 1) liver cell hydration and—consecutively—osmolyte content are modulated by hepatic nerves via an α‐adrenergic mechanism, which does not involve eicosanoids or hemodynamic changes; 2) that PC and HSC are the primary targets for nerve‐dependent α‐adrenergic activation, whereas 3) KC and SEC probably do not express α‐adrenoceptors coupled to Ca²⁺ mobilization or osmolyte efflux.