We compared diagnostic tests for keratoconjunctivitis sicca (KCS) in previously diagnosed patients and normal controls to determine the incidence of true negatives (specificity) and true positives (sensitivity). Tear osmolarity testing, the Schirmer filter paper test, and lactoferrin determination by the Lactoplate radial immunodiffusion (RID) method were performed in 20 KCS patients diagnosed on the basis of presenting symptoms and clinical examination. Similar determinations were performed in 20 age- and sex-matched normal control subjects. Mean lactoferrin concentrations in the right eyes of the KCS patients and normal controls were 134 +/- 78 (+/- 1 SD) mg/dL and 118 +/- 56 mg/dL, respectively. Tear osmolarity was 323 +/- 12 mosm/L and 306 +/- 7 mosm/L, in KCS patients and normal controls, respectively. The Schirmer test yielded a mean of 2.4 +/- 1.8 mm/minute of wetting in the KCS patients and 3.0 +/- 1.4 mm/minute in the controls. Used as a diagnostic test, lactoferrin determination by RID was found to have 35% sensitivity and 70% specificity; tear osmolarity determination had 90% sensitivity and 95% specificity; and the Schirmer test yielded 25% sensitivity and 90% specificity.