We performed measurements of the sensitivity in water of the radioguided surgery system, Neoprobe 1000. Point sources of 125I, 153Sm and 165Er were measured to a geometric accuracy of 0.1 mm. These measurements were performed with the detector uncollimated and with two different collimators; the results were used to construct three-dimensional sensitivity matrices from which isosensitivity curves could be derived. The matrices were used to simulate the reliability of detecting tumours of various sizes, at various depths, and with variable uptake ratios and activity levels of the three radionuclides investigated. Simulations showed improved tumour detection with a conical collimator, demonstrating that collimator design is important. To minimize the radiation dose during diagnostic work-up, a novel bone-seeking radiopharmaceutical, 165Er-EDTMP, was developed and tested. It showed rapid bone localization, especially in growth zones, and rapid clearance from blood and non-osseous tissues. Its biodistribution was similar to that of 153Sm-EDTMP. Based on these results and previous clinical data, the simulations predicted that lung metastases with a radius of 1 mm might be reliably detected with the Neoprobe 1000 system, if equipped with a suitable collimator.