The calculation of hydrogen bond strengths for large systems remains a computationally costly task. Here we show that the appropriate assignment of locally dense basis sets (LDBS) can greatly reduce the cost of such calculations with little or no reduction in accuracy. The use and performance of the LDBS approach with the B971 density functional and the MP2 method are demonstrated on eight small hydrogen bonded systems. Application of the LDBS approach to the adenine-thymine and cytosine-guanine nucleobase complexes shows that results of comparable accuracy to those obtained with balanced basis sets can be achieved with one to two orders of magnitude lower compute times. Similar results are obtained for complexes of tert-butylmethyl ether with five substituted phenols. (c) 2007 Elsevier B.V. All rights reserved.