The effect(s) of hypothyroidism on adult brain cognitive function are poorly understood. We performed a series of neuropsychological tests in 13 thyroid cancer patients while they continued to take their usual dose of levothyroxine (LT4) and again after discontinuing thyroid hormone. Three euthyroid subjects were also tested twice to assess the effect of repeated testing on performance. The tests assessed memory, mood, and attentional resources and controlled for the practice effects of repeated testing. The mean thyrotropin (TSH) on LT4 was 0.56 +/- 0.76 mU/L and while hypothyroid was 69 +/- 33 mU/L. While hypothyroid, the mean Beck depression score was significantly higher (15.31 +/- 9.41 hypothyroid vs. 7.31 +/- 4.82 on LT4) and the subjects rated themselves worse relative to functional memory, concentration, thinking, alertness, and motivation. Hypothyroidism was associated with a decrease in retrieval from memory (p = 0.0034), and this effect could not be attributed to depression or to practice effects. Thyroid state did not affect immediate recall, verbal learning, inhibitory efficiency, information processing speed, or attention switching. Athyrosis is associated with a decrement in delayed recall of verbal information but not in other objective measures of cognition, suggesting that the memory decrement of hypothyroidism is not caused by a generalized reduction in attentional resources.