Osmolalities of commonly administered small-volume i.v. admixtures were determined, and use of diluents with lower osmolality to achieve osmolality values less than 400 mOsm/kg was studied. The theoretical osmolality of 218 hypothetical admixtures of various concentrations of 34 injectable drugs in 50- or 100-mL quantities of 5% dextrose injection or 0.9% sodium chloride injection was calculated using sodium chloride equivalents. If the calculated osmolality value was greater than 400 mOsm/kg, an actual admixture was prepared and osmolality and density were measured. To determine how admixtures with osmolality values less than 400 mOsm/kg could be prepared, theoretical osmolality was calculated using 0.45% sodium chloride injection or sterile water for injection as the diluent. The calculated osmolality value was greater than 400 mOsm/kg for 52 (23.9%) of the 218 admixtures tested. Of the 52 measured osmolality values, 47 were within 15% of the calculated value. Calculated osmolality values for all admixtures were less than 400 mOsm/kg when 0.45% sodium chloride injection or sterile water for injection was used as the diluent. Admixture osmolality should be considered when preparing drugs for i.v. injection. For drugs with high osmolalities, 0.45% sodium chloride injection or sterile water for injection may be used as the diluent.